Is ketamine an effective treatment for depression?
It can be for some patients, says Dr. Helen Lavretsky, professor of psychiatry in-residence at the David Geffen School of Medicine at UCLA. She’s also director of the Late-Life Mood, Stress and Wellness Research Program and director of the Integrative Psychiatry Clinic. “Ketamine use should be reserved for truly treatment-resistant patients who failed to respond to two or more antidepressants administered in the optimal dose for at least two to four months,” she says.
Intravenously administered ketamine can quickly resolve “depressive symptoms and suicidal ideations” in patients under 65 years old, she says. “However, the need for IV access and physician monitoring limits its use,” Lavretsky says. In addition, the medication’s long-term use efficacy and safety are not well known.
Ketamine administered intravenously — which can involve up to six infusions — has shown positive effects in patients within a few hours, relieving depressive symptoms and suicidal thoughts, she says. Research data suggests that ketamine administered intravenously two days a week for four to six weeks can provide therapeutic benefit that can be maintained for months, says Dr. Subhdeep Virk, an associate professor of clinical psychiatry and director of the Treatment Resistant Depression Program at Ohio State University’s Wexner Medical Department of Psychiatry.
“Our clinical protocol for intravenous ketamine infusion is for starting with twice per week for three weeks as (an) acute series and then maintenance treatments once weekly, twice per week for three weeks as an acute series,” Virk says. Then, the patient would receive maintenance treatments on a weekly basis for four weeks. “After that we can stop it if the patient has significant response, or offer two more booster treatments every other week to maintain stability,” she says.
The Research on Ketamine for Depression
A review of research published in Frontiers in Neuroscience in April 2021 suggests that ketamine could “make a genuine leap forward in the therapy of depression. Its clear effectiveness in reducing symptoms of depression and suicidal ideation, either after a single administration, or especially when administered repeatedly in addition to another antidepressant, is an extremely promising factor in the treatment of depression.”
Another study, published in the Indian Journal of Psychiatry in 2019, showed that patients with depression improved rapidly and dramatically after receiving ketamine treatments. The study included 25 male patients with severe depression who were not taking any medication. They were administered six doses of ketamine over two weeks.
“There was a significant improvement in depression, anxiety and the severity of illness after two weeks and one month after the last dose of ketamine,” researchers wrote.
Research suggests that ketamine administered through the nose or taken orally requires two to four weeks of treatment before taking effect. The Food and Drug Administration approved the nasal spray esketamine — which is made of ketamine — in 2019.
Because esketamine has been approved by the Food and Drug Administration, patients who receive it must be enrolled in a Risk Evaluation and Mitigation Strategy, a drug safety program the agency can require for certain medications with serious safety concerns. The goal of the REMS program is to help ensure the benefits of the medication outweigh the risks, Virk says.
Ketamine infusions are not approved by the FDA for treatment-resistant depression.
Other Uses for Ketamine
For decades, ketamine has been used as an anesthetic and an analgesic agent both for humans and in veterinary medicine. Anesthesiologists use it as a sedative when treating patients with trauma and burns, Virk says.
Researchers initially saw antidepressant-like effects of ketamine in studies with rodents in 1975, according to research published in 2020 in Pharmacology Biochemistry and Behavior. In the 2000s, researchers began documenting the antidepressant effects of ketamine in humans.
In addition to being used as an animal tranquilizer, ketamine is also known as a club drug.
Ketamine has been used to treat pain for an array of conditions, including:
— Chronic pain.
— Neuropathic pain.
— Complex regional pain syndrome.
The Need for Caution
While the research on using ketamine to treat depression is “strong and compelling,” Virk notes, the treatment shouldn’t be viewed as a silver bullet cure. “Clinicians need to proceed with caution, as ketamine has not been tested for long-term efficacy, and its safety is unknown.”
[Read: Can Herbs Treat Depression?]
Ketamine Is not Effective for Every Patient
It’s important to keep in mind that not everyone responds to ketamine; there are no medications or supplements that affect everyone the same way. “But the remission rate of depression and the reduction in suicidal behavior are relatively high in patients who do not respond to other antidepressants,” Lavretsky says.
Patients who are treated with ketamine differ in the dose, frequency of treatment and the number of doses they need to respond to the medication. Some relapse into depression when ketamine is stopped, and some will continue to do well and maintain the effect after receiving six to eight weeks of infusions. Longer studies of ketamine use are pending.
Other Treatments for Depression
An array of other treatments are effective for many patients with depression.
Such treatments include:
— Electroconvulsive therapy and repetitive transcranial magnetic stimulation, or rTMS.
— Aerobic exercise.
— Mind-body therapies.
1. Antidepressants. Prescribing antidepressants is a mainstay of psychiatric treatment. Between 30% and 50% of patients are able to achieve remission of their depression with one antidepressant, though some people need to try a combination of medications.
FDA approved antidepressants include:
— Selective Serotonin Reuptake Inhibitors or SSRIs: Fluoxetine (Prozac), Sertraline (Zoloft), Citalopram (Celexa), Escitalopram (Lexapro), Paroxetine (Paxil), Vilazodone (Viibry) and Vortioxetine (Trinetellix).
— Serotonin Norepinephrine Reuptake Inhibitors or SNRIs: Effexor, Cymbalta, Pristiq
— Atypical Antidepressants: Mirtazapine (Remeron), Bupropion (Wellbutrin), Trazodone (Desyrel) and Nefazodone (Serzone).
— Tricyclic Antidepressants or TCAs: Amitriptyline (Elavil), Amoxapine (Asendin), Desipramine (Norpramin), Doxepin (Sinequan), Imipramine (Tofranil), Nortriptyline (Pamelor), Protriptyline (Vivactil) and Trimipramine (Surmontil).
— Tetracyclic Antidepressant: Maprotiline (Ludiomil).
— Monoamine Oxidase Inhibitors or MAOIs: Isocarboxazid (Marplan), Phenelzine (Nardil), Selegiline (Emsam) and Tranylcypromine (Parnate).
2. Psychotherapy. In particular, cognitive behavioral therapy can be effective for mild to moderate depression, Lavretsky says. It can be used in combination with antidepressants.
3. Electroconvulsive therapy and repetitive transcranial magnetic stimulation. These treatments can be administered alone or in combination with other therapies. ECT is most commonly used in patients with severe depression or bipolar disorder that haven’t responded to other treatments, according to the American Psychiatric Association. It involves a brief electrical stimulation of the brain. The patient is under anesthesia during the procedure.
rTMS employs magnetic fields to stimulate nerve cells in the brain, with the goal of improving depression symptoms.
4. Aerobic exercise. Engaging in regular exercise helps mitigate depressive symptoms. It can be used alone or in combination with antidepressants to treat mild to moderate depression.
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Update 03/15/22: The story was previously published at an earlier date and has been updated with new information.